Protective effects of sumatriptan on ischaemia/reperfusion injury following torsion/detorsion in ipsilateral and contralateral testes of rat.

This study was planned to evaluate the effects of sumatriptan, 5-HT1B/1D receptors agonist, on ischaemia/reperfusion injury in bilateral testes after unilateral testicular torsion/detorsion in rats. Male Wistar rats (n = 42) were allocated into a sham-operated group, a control group and treatment groups which were injected sumatriptan (0.1, 0.3 and 1 mg/kg), GR-127935 (0.01 mg/kg)-5-HT1B/1D receptors antagonist-and sumatriptan (0.1 mg/kg) + GR-127935 (0.01 mg/kg). Torsion was induced for 1 hr by rotating right testis 7200 in the clockwise direction, and after 7 days of detorsion, bilateral orchiectomy was conducted. While the level of TNF-α rose in testicular tissue after inducing torsion/detorsion, sumatriptan injection notably lowered TNF-α level in ipsilateral (torted) and contralateral (nontorted) testes (p < 0.001). Moreover, after inducing testicular torsion/detorsion, SOD activity was decreased, whereas administration of sumatriptan significantly increased SOD activity in bilateral testes (p < 0.001). After induction of torsion/detorsion, macroscopic and histological analyses also showed severe damages which were improved by sumatriptan injection. Interestingly, co-administration of sumatriptan with GR-127935 reversed the beneficial impacts of sumatriptan on macroscopic appearance, microscopic pattern and biochemical markers. It is concluded that sumatriptan presumably via stimulation of 5-HT1B/1D receptors decreased inflammation, oxidative stress and deteriorations induced by ischaemia/reperfusion injury following testicular torsion/detorsion.

Histological Changes in the Periosteum Following Subperiosteal Expansion in Rabbit Scalp.

PURPOSE: In intraoral bone grafting, tension-free coverage of the recipient site with periosteal flap results in optimal wound closure. Tissue expansion could be a suitable modality to obtain soft tissue in the oral cavity. The aim of this study was to assess the histology of the periosteum after subperiosteal expansion in the rabbit scalp. MATERIALS AND METHODS: In this animal study, 6 rectangular tissue expanders were placed in the skulls of 6 male white New Zealand rabbits; in 6 control rabbits, an incision was made to the periosteum but no expansion was performed. Three months after the surgeries, the rabbits were sacrificed and tissue samples were stained with hematoxylin and eosin and Masson trichrome. RESULTS: The number of osteoblasts, fibroblasts, and blood vessels and the density of collagen fibers were significantly increased in the experimental group compared with the control group (P < .001). CONCLUSIONS: Subperiosteal tissue expansion in the rabbit scalp markedly increased the histologic components of the periosteum involved in bone regeneration.

The role of clomipramine in potentiating the teratogenic effects of caffeine in pregnant rats: a histopathological study.

Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P ≤ 0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

Biochemical and histopathological evidence for the beneficial effects of modafinil on the rat model of inflammatory bowel disease: involvement of nitric oxide pathway.

BACKGROUND: Inflammatory bowel disease is an intestinal disorder presented by recurrent inflammation in the gastrointestinal tract. It has been reported that modafinil, also known as an awakening drug, has anti-inflammatory characteristics. The objective of this experiment is to investigate the protective effects of modafinil on colitis induced by acetic acid in rat and the involvement of nitric oxide pathway. METHODS: Colitis was induced by intra-rectal instillation of 1 ml acetic acid (4%). After one h of colitis induction (first day), intraperitoneal injection of dexamethasone (1 mg/kg), modafinil (50, 100, and 150 mg/kg), nitric oxide synthase inhibitors (NOS)-N (G)-nitro-L-arginine methyl ester (L-NAME) 10 mg/kg, 7-nitroindazole 40 mg/kg, and aminoguanidine 50 mg/kg-was performed and continued for 2 consecutive days. Ultimately, macroscopic, microscopic, and biochemical assessments were performed. RESULTS: While induction of colitis caused severe macroscopic lesions, administration of dexamethasone and modafinil (100 and 150 mg/kg) significantly improved macroscopic ulcers. Interestingly, the combination of modafinil with NOS inhibitors reversed the beneficial effects of modafinil on macroscopic destructions. In addition, the elevated level of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) was decreased by modafinil. However, treatment with NOS inhibitors before modafinil neutralized the anti-inflammatory influence of modafinil. Additionally, histological disorders emerged by acetic acid in colon tissue remarkably were disappeared after treatment with modafinil. CONCLUSIONS: In conclusion, modafinil has a protective effect on injuries induced by acetic acid in the colon of rat, which is presumably via the inhibition of inflammatory cascade and mediation of NO pathway.

Involvement of nitric oxide pathway in the anti-inflammatory effect of modafinil on indomethacin-, stress-, and ethanol -induced gastric mucosal injury in rat.

Gastric ulcer is a prevalent disease with various etiologies, including non-steroidal anti-inflammatory drugs (NSAIDs), stress conditions, and alcohol, resulting in an inflammatory condition in the gastric mucosa. The aim of this study was to explore the protective effects of modafinil on gastric erosions induced by indomethacin, water-immersion stress, and alcohol in rats and to evaluate the role of nitric oxide (NO) pathway. Animals were allocated to the three experimental models of gastric ulcer - indomethacin (30 mg/kg PO), water-immersion stress, and ethanol (5 ml/kg PO). Induction of gastric ulcer in all models caused an increase in J-score (macroscopic assessment), biochemical markers, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and myeloperoxidase (MPO), and microscopic destructions. Administration of modafinil (50 and 100 mg/kg i. p) significantly improved J-score in the indomethacin (P < 0.05) and stress models (P < 0.001). Moreover, the level of TNF-α IL-1ß, and MPO was deceased after modafinil administration (P < 0.001). However, modafinil did not have any effects on gastric injury induced by ethanol. In addition, co-administration of L-NAME (a non-specific NO synthase inhibitor) and aminoguanidine (an inducible NO synthase inhibitor) with modafinil significantly neutralized the gastroprotective effect of modafinil in the indomethacin and water-immersion stress groups (P < 0.05, and P < 0.01; respectively), while 7-nitroindazole (a neuronal NO synthase inhibitor) did not show such reversing effects. In conclusion, modafinil possesses gastroprotective effects on the gastric lesions induced by indomethacin and stress, which are probably mediated via the inflammation inhibition and NO pathway modulation.

Influence of Aloe Vera gel on dermal wound healing process in rat.

In this topical study the influence of Aloe Vera, on the wound healing process was investigated in 63 male rats with microscopic and cell count methods. On the day of surgery a round wound, of diameter 20 mm, was created on the back of rats necks under sterile conditions. The surgery day was determined as day zero (0). Then the rats were divided randomly into control and experimental groups 1 and 2. Animals in each group were sub-divided to three smaller groups, investigated every 4, 7, and 14 days. From day 0, wound surfaces were covered with gel once daily in experimental group 1 and twice daily, for 12 h interval, in experimental group 2. Each rat received 30 g of the gel. The wound surface and healing were assessed on days 4, 7, and 14, and then a sample from the wound was prepared and investigated microscopically. The results show that the number of neutrophil, macrophage, and fibroblast cells and the wound thickness in the control group were statistically different from the experimental groups. It was found that the wound diameter thickness in the experimental group was greatly lower due to twice administration of gel and the power of wound healing was more than other groups.

Beneficial effects of dapsone on ischemia/reperfusion injury following torsion/detorsion in ipsilateral and contralateral testes in rat.

Testicular torsion is a serious urologic emergency and one of the causes of infertility in males. Hence, prompt diagnosis and treatment are important to prevent testicular damages. It has been proved that dapsone (4, 40 diamino-diphenyl sulfone) has anti-oxidative and anti-inflammatory effects. Therefore, the aim of this study was to investigate the influence of dapsone on ischemia/reperfusion (I/R) injury in bilateral testes after unilateral testicular torsion/detorsion (T/D) in rats. In this experiment, eighteen male Wistar rats were allocated into three groups, including sham-operated, T/D + vehicle, and T/D + dapsone (12.5 mg/kg). Testicular torsion was induced for 1 h by rotating right (ipsilateral) testis 7200 in the clockwise direction. After 7 days of reperfusion, bilateral orchiectomy was conducted and evaluations of biochemical markers - tumor necrosis factor alpha (TNF-α) and superoxide dismutase (SOD) - and histological changes were performed. While induction of testicular T/D remarkably increased the level of TNF-α in the ipsilateral (torted) and contralateral (non-torted) testes, intraperitoneal (i.p) administration of dapsone (12.5 mg/kg) significantly lowered the TNF-α level (p < 0.001). Additionally, after induction of T/D, SOD activity was notably decreased, whereas administration of dapsone (12.5 mg/kg, i.p.) significantly raised SOD activity in the bilateral testes (p < 0.001). I/R injury also caused lesions in the microscopic pattern of the bilateral testicular tissues, while administration of dapsone (12.5 mg/kg, i.p.) led to a significant improvement in testicular damages. It was concluded that dapsone had a protective impact on I/R injury in the rat model of testicular T/D, and this effect was most likely induced by anti-inflammatory and anti-oxidative properties of dapsone.

The Teratogenic Effects of Flurazepam Intake during Organogenesis of the Rat Fetus.

ABSTRACT Flurazepam is a long acting drug with sedative, hypnotic, anxiolytic, relaxant, and anti-epileptic properties. The drug is a benzodiazepine and is commonly used by adults, including pregnant women, intentionally or sometimes unintentionally during their pregnancy. It is increasingly used these days, and therefore, it seems a special problem to the clinician treating anxiety disorders in women. It should be noticed that flurazepam exposure during pregnancy may have teratogenic effects on the fetus. Until now, many studies have been conducted on drug side-effects in poisonings, behavioral disorder, and anxiety reactions, but there is no accurate report about the teratogenic effect of flurazepam. In this study, teratogenicity flurazepam intake during pregnancy and its effects on fetus development was investigated. About 30 virgin rats of known age and weight were used. After being pregnant, they were divided into three groups: Negative and positive control group, case groups exposed for 1 to 6 mg/kg/day. The fetuses were first studied macroscopically regarding anomalies, and then histological and histochemically to inspect the defects of tissue organogenesis. Our results show that there was significant difference in the weight and length of the cases compared to the control group. The statistical results indicate that flurazepam intake during the second half of pregnancy can lead to irreversible anomalies. It seems that benzodiazepine therapy among pregnant woman would be better to avoid during the first trimester and multidrug regimens.

Impacts of morphine addiction on spermatogenesis in rats.

BACKGROUND: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. OBJECTIVE: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. MATERIALS AND METHODS: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. RESULTS: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p<0.05). Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0) and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001). CONCLUSION: Morphine could affect all spermatogenesis stages.

Trimetazidine prevents oxidative changes induced in a rat model of sporadic type of Alzheimer's disease.

Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg) after which injected with intracerebroventricular-streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1) expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA) level. TMZ administration also increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer's disease and possible prevention of disease progression.

Teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses.

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P ≤ 0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.

Effect of Trolox addition to cryopreservation media on human sperm motility.

BACKGROUND: Sperm parameters and motion kinetics are affected by cryopreservation. OBJECTIVE: The main purpose of the current study was to determine the effect of different concentrations of Trolox as an antioxidant to freezing-thawing procedure on human sperm kinematic parameter. MATERIALS AND METHODS: Semen was collected from 20 normal donors and divided into five aliquots prior to cryopreservation. The first aliquot was analyzed by computer-assisted sperm analysis (CASA). Other aliquots were mixed with cryo-protective agent containing 0, 20, 40, and 80 µmol Trolox and treated samples were cryopreserved in liquid nitrogen. After two weeks samples were thawed and sperm motion kinematics was measured by CASA. Percent motility (Mot), curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), and amplitude of lateral head displacement (ALH) were compared before and after freeze. RESULTS: Addition of 40µmol Trolox resulted in significantly higher (p<0.05) post thaw VCL, VSL and VAP compared to other groups. Therefore the percentage of post thaw motile spermatozoa were significantly higher (p<0.01). CONCLUSION: The supplementation of Trolox significantly improved the post-thawed human semen quality, especially progressive motility and average path velocity.

The effect of Achillea millefolium extract on spermatogenesis of male Wistar rats.

Achillea millefolium or yarrow, a native plant in many countries, has been recognized in historical medicine, mainly because of its astringent effects. However, some aspects of the toxicity of yarrow such as possible effects on male reproductive system are not well established. In this investigation, the effects of A. millefolium L. extract on spermatogenesis in adult male wistar rats were studied. Eighty-five male Wistar rats were divided into nine experimental groups (10 in each group except the ninth group). Extract was administered at the dose of 200, 400 and 800 mg/kg/day by intraperitoneal (IP) injection or through gavage for 22 days, on every other day. Three groups were determined as sham and control groups. Five rats from each group were killed and the rest of the rats were kept for 40 days later, but with no injection, to assess the reversibility of extract effect on spermatogenesis. The results of the study showed scattered immature cells on basal membrane in seminiferous tubules at the dose of 400 mg/kg/day IP. Moreover, a significant decrease in cell accumulation and vacuolization in seminiferous tubule was seen. At the dose of 800 mg/kg, IP, thickened seminiferous tubules on basal membrane, decrease in cell accumulation in seminiferous tubule, severe disarrangement, degenerative cells and severe decrease in sperm count were seen. At the dose of 800 mg/kg/day, orally, basal membrane was thickened and the disarrangement in cells was demonstrated. As a conclusion, our results suggest that the total extract of A. millefolium L. exhibit temporary antifertile activity in adult male animals.